Curcumin encapsulated in milk small extracellular vesicles as a nanotherapeutic alternative in experimental chronic liver disease
Open accessAbstract
Curcumin is a natural molecule widely tested in preclinical and clinical studies due to its antioxidant and anti-inflammatory activity. Nevertheless, its high hydrophobicity and low bioavailability limit in vivo applications. To overcome curcumin´s drawbacks, small extracellular vesicles (sEVs) have emerged as potential drug delivery systems due to their non-immunogenicity, nanometric size and amphiphilic composition. This work presents curcumin cargo into milk sEV structure and further in vitro and in vivo evaluation as a therapeutic nanoplatform. The encapsulation of curcumin into sEV was performed by two methodologies under physiological conditions: a passive incorporation and active cargo employing saponin. Loaded sEVs (sEVCurPas and sEVCurAc) were fully characterized by physicochemical techniques, confirming that neither methodology affects the morphology or size of the nanoparticles (sEV: 113.3±5.1 nm, sEVCurPas: 127.0±4.5 nm and sEVCurAc: 98.5±3.6 nm). Through the active approach with saponin (sEVCurAc), a three-fold higher cargo was obtained (433.5 µg/mL) in comparison with the passive approach (129.1 µg/mL). These sEVCurAc were further evaluated in vitro by metabolic activity assay (MTT), confocal microscopy, and flow cytometry, showing a higher cytotoxic effect in the tumoral cells RAW264.7 and HepG2 than in primary hepatocytes, specially at high doses of sEVCurAc (4%, 15% and 30% of viability). In vivo evaluation in an experimental model of liver fibrosis confirmed sEVCurAc therapeutic effects, leading to a significant decrease of serum markers of liver damage (ALT) (557 U/L to 338 U/L with sEVCurAc therapy) and a tendency towards decreased liver fibrogenesis and extracellular matrix (ECM) deposition.
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Small molecule drugs, such as curcumin and paclitaxel, can be co-incubated with parent cells for loading into EVs.
“Small molecule drugs, such as curcumin and paclitaxel, can be co-incubated with parent cells at various conditions for loading into EVs [217, 218].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [217]
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- Authors
- Albaladejo-García, V., Morán, L., Santos-Coquillat, A., González, M. I., Ye, H., Vázquez Ogando, E., Vaquero, J., Cubero, F. J., Desco, M., & Salinas, B.
- Affiliations
- Universidad Complutense de Madrid (ES)
- Spanish National Centre for Cardiovascular Research (ES)
- Hospital General Universitario Gregorio Marañón (ES)
- Instituto de Salud Carlos III (ES)
- Corresponding author
- Desco, Manuel
- Salinas, Beatriz
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2024-04
- Volume
- 173
- Pages
- 116381
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W4392543522
- Cited by
- 32
- References
- 49
- Citations by year
- 2026: 15 · 2025: 15 · 2024: 2
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Ministerio de Ciencia e Innovación (CD19/00136)
- Instituto de Salud Carlos III (PI20/01632)
- European Social Fund Plus (PEJD-2018-POST/BMD-9592, PEJD-2018-PRE/BMD-9405)
- Comunidad de Madrid (S2022/BMD-7403 RENIM-CM, EXOHEP2-CM, S2022/BMD-7409)
- Horizon 2020 (101095679, HORIZON-HLTH-2022-STAYHLTH-02)
- Consejería de Educación e Investigación
- European Regional Development Fund
- Gobierno de España Ministerio de Ciencia, Innovación y Universidades (PID2020-117941RB-I00)
- Universidad Carlos III de Madrid (CRUE-Madro\u00F1o 2024)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Curcumin's Biomedical Applications
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- curcumin, small extracellular vesicles, drug encapsulation, chronic liver disease, liver fibrosis, nanotherapeutics, hepatoprotection, extracellular matrix deposition, RAW 264.7 macrophages, HepG2 cells
- MeSH terms
- Extracellular Vesicles, Animals, Curcumin, Humans, Liver Cirrhosis, Milk, Saponins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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